Mechanism of regulating immune dysfunction of sepsis based on network pharmacology and experimental verification / 中国药理学通报

Aim To verify the role of Shengjiang Powder in sepsis and explore its molecular mechanism. Methods The targets of drug active ingredients and disease-related targets were searched by TCMSP, Disgenet and other databases, and the intersection of the two was selected. DAVID database was used to carry out enrichment analysis of GO and KEGG pathways for intersection targets, and molecular docking was performed between drug active ingredients and core genes of key pathways. Mouse model of sepsis was constructed by cecal ligation puncture (CLP). Spleen tissue and serum of mice were collected. The percentage of T cell subsets in spleen was detected by flow cytometry, and IL-6 and IL-10 levels in serum were detected by ELISA. Results A total of 25 active ingredients, 238 targets of active ingredients, 2797 disease-related targets, 90 genes of intersection between active ingredients and disease-related targets, potential targets were AKT, JUN, EGFR, MMP9, etc. GO enrichment analysis showed 1021 items, including 942 biological processes, 23 cell compositions and 55 molecular functions. KEGG pathway analysis found that the intersection genes were mainly enriched in THE PD-1/PD-L1 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway and inflammatory mediators signaling pathway, indicating that the therapeutic effect may be related to these pathways. The molecular docking results showed that quercetin, kamanol, emodin and other core compounds could be well combined with key genes. Flow cytometry results showed that after seven days of CLP, the proportion of CD4 T cells in spleen decreased, the proportion of CD4 PD-1 T cells increased, the release of IL-6 decreased, the content of IL-10 increased, and the mice were immunosuppressed. The percentage of CD4 T cells in spleen increased, the number of CD4 PD-1 T cells decreased, the release of IL-6 was enhanced, the content of IL-10 decreased, and the immunosuppression was improved. Conclusions It is proved that Shengjiang Powder can increase the release of pro-inflammatory cytokine IL-6, increase the ratio of CD4 T/CD8 T cells, and decrease the expression of anti-inflammatory cytokine IL-10 in the late stage of sepsis, so as to improve immune suppression in the late stage of sepsis and improve the survival rate of mice.

Mechanism of Shengjiang Powder in treating chronic tonsillitis in children based on network pharmacology and molecular docking / 中国中药杂志

Based on the network pharmacology and molecular docking method to explore the molecular mechanism of Shengjiang Powder in treating chronic tonsillitis in children. This research first based on the Traditional Chinese Medicine System Pharmacology(TCMSP) and the Bioinformatics Analysis Tools for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM), the effective active ingredients of the drugs contained in Shengjiang Powder were screened out by the pharmacokinetic(ADME) parameters, the targets were predicted, and then chronic tonsillitis disease in children targets were obtained by GeneCards database. Afterwards, the target protein names were standardized by the Uniprot database. The drug targets were matched with the disease targets to obtain the potential therapeutic targets of Shengjiang Powder. Cytoscape 3.8.0 software was used to screen out and construct the network diagram of "drug-components-core targets-disease". DAVID database and R language were used to conduct the enrichment analysis of core action targets. Finally, AutoDock software was used to conduct molecular docking between drug components with a high network medium value and core action targets. According to the findings, after standardized treatment, a total of 79 active ingredients of Shengjiang Powder were obtained; it was predicted to get 1 261 potential targets, 268 potential targets for treatment of chronic tonsillitis in children, and 29 core targets; and 81 entries of GO enrichment were determined(P<0.05), including 63 biological processes, 7 cell components, 11 molecular function items, 24 KEGG pathway enrichment items(P<0.05), mainly including cell cycle, inflammatory factors, viral infection, immune regulation and other signaling pathways. The results of molecular docking showed that main active components in Shengjiang Powder had a stable binding activity with the core targets. This study revealed the mechanism of Shengjiang Powder in the treatment of chronic tonsillitis in children, mainly by resisting virus, inhibiting inflammation, regulating immunity and other means to play a synergistic effect, so as to provide a theoretical basis for rational clinical application.

Shengjiang Powder ameliorates myocardial injury in septic rats by downregulating the phosphorylation of P38-MAPK

Sepsis is the systemic inflammatory response caused by infection. Cardiac dysfunction is an acknowledged result of sepsis.Shengjiang Powder, a prescribed traditional Chinese medicine, showed anti-infection and antipyretic functions in ourprevious study. In this study, we established a septic rat model via cecal ligation puncture (CLP) to evaluate the effects ofShengjiang Powder on sepsis and the involvement of P38 mitogen activated protein kinase (P38-MAPK) signaling. The 10main ingredients of Shengjiang Powder were identified by LC–MS. The results of this study indicated that ShengjiangPowder at a concentration of 3.0 g/kg with SB203580 (an inhibitor of P38-MAPK) could improve myocardial injury,ameliorate the histopathological abnormalities, decrease apoptosis and upregulate proliferating cell nuclear antigen (PCNA)levels in myocardial tissues. Further, cytokine mRNA expression levels (tumor necrosis factor - alpha, TNF-a and interleukin 6, IL-6) were decreased by Shengjiang Powder and SB203580 in the myocardial tissues. Furthermore, the p-P38protein level in myocardial tissues was upregulated in septic rats but decreased upon treatment with Shengjiang Powder andSB203580; however, the relative protein level of P38 showed no significant changes. Collectively, Shengjiang Powdershowed a myocardial protective effect on rats with CLP-induced sepsis.

Experimental Study of Shengjiang Powder on Treating Acute Lung Injury / 广州中医药大学学报

Objective To investigate the therapeutic mechanism of Shengjiang Powder(SP)on acute lung injury.Methods Forty healthy SD male rats were divided into 3 groups randomly: normal group,model group,and SP group.After administration for 6 days,acute lung injury rat models were established by injecting lipopolysaccharide(LPS)into sublingual vein.Lung histological sections were prepared for the detection of NF-?B expression by immmunohistochemistry.The images of the lung histological sections were captured and the average gray values of nucleus of endothelial cells in lung micrangium were measured.Results Compared with the model group,SP could depress the expression of NF-?B in the nucleus of lung microvascular endothelial cells,and statistical difference existed between the two groups(P